Infectious bovine rhinotracheitis (IBR) was first recognized as a distinct disease of cattle during the 1950's. Consistent with the characteristics of other herpesviruses, IBR virus (IBRV) replicates in a wide range of cell types and produces diverse disease manifestations which include respiratory tract disease, conjunctivitis, vulvovaginitis, abortion, balanoposthitis, meningoencephalitis, alimentary tract disease and fatal systemic infection. However, IBR is known mainly as a respiratory tract disease characterized by tracheitis, rhinitis, and fever. IBR infection is the most commonly diagnosed cause of abortion in pregnant cattle. See Kirkbride et al, J. Am. Vet. Med. Assoc., 162, 556-560 (1973). The virus is readily transmitted and has worldwide distribution. Some cattle develop a latent infection, which can be reactivated.
Control of IBR is based largely on vaccination, and a number of different kinds of IBR vaccines have been developed. See Kahrs, J. Am. Vet. Med. Assoc., 171, 1055-1060 (1977). These include parenteral and intranasal vaccines, both of which use live attenuated IBRV. The parenteral vaccines, which are usually administered intramuscularly, may cause abortion in pregnant cattle, and are therefore contraindicated for pregnant cattle. Further, vaccination of suckling calves which are nursing pregnant cattle may cause abortion due to the shedding of virus by the vaccinated calves. Intranasal vaccines are safer in these respects, and are capable of producing humoral antibodies at titers comparable with those of intramuscular vaccines. However, there are problems associated with administration of intranasal vaccines. Head restraint is required, and care must be taken to administer the vaccine deeply into both nostrils. There is a tendency for vaccinated animals to blow the vaccine out when they snort after vaccination.
The degree of efficacy of prior art vaccines is variable, and the duration of protection is limited. In general, it is believed that intramuscular vaccination gives protection of longer duration than intranasal vaccination. With intranasal vaccination, conservative practice dictates annual revaccination, while at least occasional revaccination is recommended with the intramuscular vaccines. Inactivated IBR vaccines have also been developed, but there is controversy about their effectiveness. Annual revaccination is recommended. Further disadvantages of inactivated vaccines include concern for fatal hypersensitivity reaction (anaphylaxis) and nonfatal urticaria.
Heretofore no subunit IBR vaccine has been reported. However, a subunit approach to the preparation of some other virus vaccines has been explored. See, for example, Rubin et al, Progr. Med. Virol., 21, 144-157 (1975). Cappel has reported experiments with a subunit vaccine of herpes simplex virus in rabbits. Arch. Virol. 52, 29-35 (1976). The subunit vaccine was found as effective as immunization with live or U.V inactivated herpes simplex virus. Similarly, Cox et al have reported experiments with a subunit vaccine for human rabies. Infect. and Immun., 16, 753-754 (1977). Both Cappel and Cox et al worked with non-ionic detergent extracts of the virions, since it is known that non-ionic detergents are capable of solubilizing envelope glycoproteins of viruses. See Helenius et al, "Solubilization of Membranes by Detergents", Biochem. et Birphys. Acta, 415, 29-79 (1975). However, Sokal stated as a general rule that subunit vaccines containing soluble antigens would be epxected to provide a specific immunogenicity or specific protective action which is markedly lower than that of virion vaccines. Sokal, Vaccines of the Future: Immunogenicity of Viral Components, Chapt. 9, pp. 129-135, in Viruses and Immunity, Koprowski and Koprowski, 1975, Academic Press, Inc..